Personalized oncology has the potential to revolutionize the way cancer patients will be treated in the future. Different entities of cancer can be divided into subclasses based on molecular differences, including the specific activation of signaling pathways that often determine therapy response and clinical outcome. For various cancer entities including breast, lung and colon cancer, the identification of such subtypes and the possibility to stratify patients into cohorts has already been translated into clinical practice to treat patients in a subtype-specific manner.
PDAC is the most frequent pancreatic cancer and the fourth cause of cancer death in the United States and Europe. Most patients die within 12 months, and only 2% survive five years after prognosis. Little progress in the treatment of PDAC has been made since the approval of gemcitabine in 2000. Apart from gemcitabine (Burris et al., 1997), the recently described FOLFIRINOX scheme (Conroy et al., 2011) and the albumin-paclitaxel conjugate nab-paclitaxel (Von Hoff et al., 2013), treatment options are limited despite extensive research and the discovery of several promising drug candidates (Costello et al., 2012). In a range of tumor types targeted therapies have been successfully implemented (Vanneman and Dranoff, 2012; Zhang et al., 2009). However, these have shown little or no survival benefit for PDAC patients (Hidalgo, 2010; Vincent et al., 2011). One exception is the epidermal growth factor receptor (EFGR) tyrosine kinase inhibitor, erlotinib, which was approved in 2005 and which slightly improves survival in combination treatment with gemcitabine (Moore et al., 2007).
PDAC is still classified as a single cancer entity and is clinically treated as such. However, the existence of three PDAC subtypes termed classical, quasi-mesenchymal (QM-PDA) and exocrine-like has recently been suggested (Collisson et al., Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 17 (2011) 500-503). The identification of these subtypes was initially based on comparative gene expression analysis in micro-dissected epithelial cells form patient specimens. In a large panel of human and murine tumor cell lines only the classical and the QM-PDA subtypes were identified, while no cell line modeled the exocrine-like subtype (Collisson et al., 2011). Recently, a cell line model for the exocrine-like subtype has been developed, and specific biomarkers and/or biomarker patterns have been identified for each of the three subtypes (see WO 2014/056626).
The existence of PDAC subtypes and the possibility to identify such subtypes based on biomarker analysis raises the possibility of identifying inter-subtype specific differences regarding the sensitivity to therapeutic agents. Initially, the classical and the QM-PDA subtype were shown to differ in their response to gemcitabine and erlotinib, while the drug sensitivity of the exocrine-like subtype had yet to be determined (Collisson et al., 2011). The development of a cell line model for the exocrine-like subtype, and the identification of specific biomarkers and/or biomarker patterns (WO 2014/056626) can now be used to stratify patients and to establish individualized therapy approaches for PDAC (see WO 2014/056627).
Thus, despite certain progress that has been made in the characterization and sub-typing of cancers, particularly of PDAC, and the development of stratification and treatment approaches based on such developments, there is still a great need for the development of additional and/or refined methods for cancer patient stratification and the development of more efficient treatment schemes.
The solution to this problem, i.e. the sub-typing of cancers based on the metabolic status of the cancer cells, and the identification of therapeutic approaches that modify and/or interfere with such metabolic status, are neither provided nor suggested by the prior art.